SapC-DOPS is a novel nanotherapeutic that has been shown to target and induce cell death in a variety of cancers, including glioblastoma (GBM). GBM is a primary brain tumor known to frequently demonstrate resistance to apoptosis-inducing therapeutics. Here we explore the mode of action for SapC-DOPS in GBM, a treatment ...

Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and ...

While multiple rodent pre-clinical studies, and to a lesser extent human clinical trials, claim the feasibility, safety and potential clinical benefit of cell grafting in the central nervous system (CNS), currently only little convincing knowledge exists regarding the actual fate of the grafted cells and their effect on the surrounding ...

Hayakawa Kentaro K Department of Rehabilitation for Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan; Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, - - 2014

The inflammatory response following spinal cord injury (SCI) has both harmful and beneficial effects; however, it can be modulated for therapeutic benefit. Endotoxin/lipopolysaccharide (LPS) preconditioning, a well-established method for modifying the immune reaction, has been shown to attenuate damage induced by stroke and brain trauma in rodent models. Although such ...

The family of interleukin (IL)-6 like cytokines plays an important role in the neuroinflammatory response to injury by regulating both neural as well as immune responses. Here, we show that expression of the IL-6 family member oncostatin M (OSM) and its receptor is upregulated after spinal cord injury (SCI). To ...

Polyphenols have been shown to have some of the neuroprotective effects against neurodegenerative diseases. These effects are attributed to a variety of biological activities, including free radical scavenging/antioxidant and anti-inflammatory and anti-apoptotic activities. In this regard, many efforts have been made to study the effects of various well-known dietary polyphenols ...

Both chronic and acute inflammatory circuits are known to be associated with malignancy and drug resistance indicating that many antiinflammatory agents can potentially act as chemotherapeutic drugs. A series of new class of propanediones with good antiinflammatory activity were shown to possess moderate cytotoxic activities. The aim of the study ...

Context Inflammation after spinal cord injury (SCI) may be responsible for further neural damages and therefore inhibition of inflammatory processes may exert a neuroprotection effect. Objectives Here, we tried to assess the efficacy of some non-conventional herbal medications including sulforaphane, tanshinone IIA, and tetramethylpyrazine in reducing inflammation and compare them ...

Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs. That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM-affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, ...

Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial ...

Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organised inflammatory response to injury. Intricate immune cell interactions are triggered, typically consisting of ...

Stoolman Joshua S JS Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; - - 2014

The adoptive transfer of myelin-reactive T cells into wild-type hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem inflammation and ataxia, which characterize disease in IFN-γRKO hosts (atypical EAE). In this article, we show that atypical EAE correlates ...

Immunostimulation by anticancer cytotoxic drugs is needed for long-term therapeutic success. Activation of dendritic cells (DCs) is crucial to obtain effective and long-lasting anticancer T-cell mediated immunity. The aim of this study was to explore the effect of capsaicin-mediated cell death of bladder cancer cells on the activation of human ...

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Macrophages and microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor ...

Cox April A Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas ST. MSC606, Charleston, SC, 29425, USA, - - 2014

A need exists for the effective treatment of individuals suffering from spinal cord injury (SCI). Recent advances in the understanding of the pathophysiological mechanisms occurring in SCI have resulted in an expansion of new therapeutic targets. This review summarizes both preclinical and clinical findings investigating the mechanisms and cognate pharmacologic ...

Actin cytoskeleton is a main target of many bacterial pathogens. Among the multiple regulation steps of the actin cytoskeleton, bacterial factors interact preferentially with RhoGTPases. Pathogens secrete either toxins which diffuse in the surrounding environment, or directly inject virulence factors into target cells. Bacterial toxins, which interfere with RhoGTPases, and ...

Systemic and local infections and inflammations are known to cause infertility in humans and animals. However, the mechanisms by which infection/inflammation induces infertility are only partially known. The objectives of this study were: (i) to provide models of systemic (acute) and local (sub-acute) inflammation by intra-peritoneal injection or intra-cervical deposition ...

The cell-cycle inhibitor flavopiridol has been shown to improve recovery from spinal cord injury in animal models. However, the systemic dose of flavopiridol has side-effects and the mechanism of action is not clear. This study aimed to develop a strategy for the local delivery of flavopiridol and investigate its mechanisms ...

Greenhalgh Andrew D AD Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada, H3G - - 2014

Macrophages in the injured spinal cord arise from resident microglia and infiltrating, peripherally derived monocytes. It is still not clear if macrophages derived from these two populations differ in their roles after CNS injury. The aims of this study are to investigate the phagocytic response and clearance of damaged axons ...

Canine intervertebral disk herniation (IVDH) is a common, naturally-occurring form of spinal cord injury (SCI) which is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury ...

Tzekou Apostolia A Toronto Western Research Institute and Krembil Neuroscience Centre, University Health Network, University of Toronto, Toronto, - - 2014

Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in ...

Chronic spinal cord compression is the result of mechanical pressure on the spinal cord, which in contrast to traumatic spinal cord injury, leads to slowly progressing nerve degeneration. These two types of spinal cord injuries may trigger similar mechanisms, including motoric nerve cell apoptosis and autophagy, however, depending on differences ...

CD36 is a pleiotropic receptor involved in several pathophysiological conditions, including cerebral ischemia, neurovascular dysfunction and atherosclerosis, and recent reports implicate its involvement in the endoplasmic reticulum stress response (ERSR). We hypothesized that CD36 signaling contributes to the inflammation and microvascular dysfunction following spinal cord injury. Following contusive injury, CD36(-/-) ...

Human papillomavirus (HPV) is the primary cause of cervical cancer and genital warts. The development of HPV vaccines has been a major advance in the prevention of these diseases. Recent studies have shown promising early effects of HPV immunization programs on cervical abnormalities and genital warts, with evidence of herd ...

Immune responses in the uterine cervix are considered to play an important role in persistent human papillomavirus (HPV) infection and carcinogenesis, but many aspects of the mechanism are still unclear. The goal of this study was to measure cytokines to analyze immune responses in patients with cervical intraepithelial neoplasia (CIN). ...

Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. The M. abscessus rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth ...

Spinal cord injury (SCI) is a common and serious trauma which lacks efficient treatment. Inhibition of cell death in the trauma area is important for spinal cord protection during this process. In this study, necroptosis inhibitor necrostatin-1(Nec-1) was used to treat the SCI rats, to investigate the role of Nec-1 ...

Schwann cells (SCs) are the major cells constituting the peripheral nerve structure and function, and also secret a variety of neurotrophic factors. Schwann cell (SC) transplantation has recently emerged as a promising therapeutic strategy for spinal cord injury (SCI). In the present study, the ability of genetically modified SCs producing ...

Spinal cord injury is a debilitating condition that affects motor, sensory and autonomic functions. Subsequent to the first mechanical trauma, secondary events, which include inflammation and glial activation, exacerbate tissue damage and worsen functional deficits. Although these secondary injury mechanisms are amenable to therapeutic interventions, the efficacy of current approaches ...

To explore whether hypoxia and interleukin 8 (IL-8) regulate the viability and apoptosis of cervical carcinomas cells and the possible mechanism. We evaluated the expression of hypoxia inducible factor-1α (HIF-1α), IL-8 and its receptors (CXCR1 and CXCR2) in cervical cancer and cervicitis tissues by immunohistochemistry. Then the effects of hypoxia ...

Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect the ...

Juno Jennifer A JA Department of Medical Microbiology, University of - - 2014

Despite the public health importance of mucosal pathogens (including HIV), relatively little is known about mucosal immunity, particularly at the female genital tract (FGT). Because heterosexual transmission now represents the dominant mechanism of HIV transmission, and given the continual spread of sexually transmitted infections (STIs), it is critical to understand ...

The receptor-interacting protein kinase 3 (RIP3) associates with RIP1 in a necrosome complex that can induce necroptosis, apoptosis, or cell proliferation. We analyzed the expression of RIP1 and RIP3 in CD34+ leukemia cells from a cohort of patients with acute myeloid leukemia (AML) and CD34+ cells from healthy donors. RIP3 ...

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced ...

P-glycoprotein (P-gp) is a major factor in multidrug resistance (MDR) which is a serious obstacle in chemotherapy. P-gp has also been implicated in causing apoptosis of tumor cells, which was shown to be another important mechanism of MDR recently. To study the influence of P-gp in tumor cell apoptosis, K562/A ...

The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kruppel-like factor 4 (klf4) is a zinc finger- containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, ...

It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro ...

The modulation of host cell apoptosis by bacterial pathogens is critical for their intracellular survival. Several intracellular bacteria achieve this by secreting proteins that interact with apoptosis pathways to inhibit host cell apoptosis. Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis, is such bacterium. The protein Ats-1, translocated from A. phagocytophilum ...

Reactive nitrogen is critical for the clearance of Francisella tularensis infections. Here we assess the role of nitric oxide in control of intracellular infections in two murine macrophage cell lines of different provenance: the alveolar macrophage cell line, MH-S, and the widely used peritoneal macrophage cell line, J774A.1. Cells were ...

Gossypol is a phenolic aldehyde extracted from plants and is known to be an antitumor agent to induce cancer cell apoptosis. In the present study, multiple myeloma cells were treated with gossypol, which resulted in an increase of cellular reactive oxygen species (ROS) and cell necrosis. Quantitative proteomic analysis was ...

Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation ...

Macrophages, as key players of the innate immune response, are at the focus of research dealing with tissue homeostasis or various pathologies. Transfection with siRNA and plasmid DNA is an efficient tool for studying their function, but transfection of macrophages is not a trivial matter. Although many different approaches for ...

To investigate the anti-proliferative mechanism of mangiferin in a human nasopharyngeal carcinoma cell line, CNE2 cells were incubated with different concentrations of mangiferin (12.5, 25, 50, 100, 150 and 200 μM) or with PBS as a control for 72 hours. Analyses were made of the cell cycle and apoptosis with ...